Streptonigrin Mitigates Lung Cancer-induced Cachexia by Suppressing TCF4/TWIST1-induced PTHLH Expression.

Autor:	Fang XQ; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea., Lee S; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea., Kim YS; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea.; Jung-Ang Microbe Research Institute (JM), Heungdeok-gu, Cheongju, Republic of Korea., Han GE; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea., Lim CH; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea., Lim JH; Department of Medicinal Biosciences, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea; jhlim@kku.ac.kr.; Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju, Republic of Korea.; Center for Metabolic Diseases, Konkuk University, Chungju, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Anticancer research [Anticancer Res] 2023 Mar; Vol. 43 (3), pp. 1149-1157.
DOI:	10.21873/anticanres.16260
Abstrakt:	Background/aim: Cachexia - a wasting disorder of adipose and skeletal muscle tissue - is the most common driver of poor prognosis in patients with advanced lung cancer. Parathyroid hormone-like hormone (PTHLH) is potentially a critical factor in cancer-associated cachexia. We previously showed that streptonigrin - an aminoquinone with antitumor effects - inhibited the interaction between TCF4 and TWIST1. This study aimed to determine the anti-cachectic performance of streptonigrin in lung cancer. Materials and Methods: We assessed the effect of streptonigrin on the interaction of TCF4 and TWIST1 using co-immunoprecipitation and a mammalian-two hybrid luciferase assay, which was confirmed by an in vitro GST pull-down assay using recombinant bHLH domain-containing TCF4 and TWIST1. We assessed the anti-cachectic effect of streptonigrin in vivo using an LLC1 cell-induced tumour-bearing mouse model. Changes in the degree of skeletal muscle and adipose tissue wasting were determined by measuring the weights of gastrocnemius and epidydimal white adipose tissue. Results: Streptonigrin was found to inhibit the interaction of TCF4 with TWIST1 in a dose-dependent manner. The in vitro GST pull-down assay revealed that streptonigrin directly inhibited the interaction between TCF4 and TWIST1. The expression of PTHLH mRNA, which is transcriptionally regulated by the TCF4/TWIST1 complex in response to TGF-β1 signalling, was decreased in streptonigrin-treated lung cancer cells. Streptonigrin significantly decreased the expression of proteolysis-related genes in skeletal muscle and browning-related genes in white adipose tissues of LLC1-induced tumour-bearing mice. Conclusion: Streptonigrin exerts potent therapeutic effects on lung cancer-induced cachexia by suppressing TCF4/TWIST1-mediated PTHLH expression. (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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